Study Assessing Saxagliptin Treatment In Type 2 Diabetic Subjects Who Are Not Controlled With Metformin Alone

This study has been completed.
Sponsor:
Information provided by:
AstraZeneca
ClinicalTrials.gov Identifier:
NCT00121667
First received: July 18, 2005
Last updated: June 4, 2014
Last verified: June 2014
  Purpose

The purpose of this clinical research study is to learn whether Saxagliptin added to Metformin therapy is more effective than Metformin alone as a treatment for type 2 diabetic subjects who are not sufficiently controlled with Metformin alone


Condition Intervention Phase
Diabetes Mellitus, Type 2
Drug: Saxagliptin + Metformin
Drug: Placebo + Metformin
Drug: Pioglitazone
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: "A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Phase III Trial to Evaluate the Efficacy and Safety of BMS-477118 in Combination With Metformin in Subjects With Type 2 Diabetes Who Have Inadequate Glycemic Control on Metformin Alone"

Resource links provided by NLM:


Further study details as provided by AstraZeneca:

Primary Outcome Measures:
  • Baseline and Change From Baseline in Hemoglobin A1c (A1C) at Week 24 [ Time Frame: Baseline, Week 24 ] [ Designated as safety issue: No ]
    Mean change from baseline is adjusted for baseline value.


Secondary Outcome Measures:
  • Baseline and Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24 [ Time Frame: Baseline, Week 24 ] [ Designated as safety issue: No ]
    Mean change from baseline is adjusted for baseline value.

  • Percentage of Participants Achieving Therapeutic Glycemic Response (A1C < 7.0%) at Week 24 [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
  • Baseline and Change From Baseline at Week 24 in Postprandial Glucose (PPG) Area Under the Curve (AUC) [ Time Frame: Baseline, Week 24 ] [ Designated as safety issue: No ]
    Mean change from baseline is adjusted for baseline value.


Other Outcome Measures:
  • Overall Summary of Adverse Events During ST+LT Treatment Period [ Time Frame: AEs: up to last treatment day + 1 day or last visit day in the ST+LT period; SAEs: up to last treatment day + 30 days or last visit day + 30 days in the LT+ST period. Mean duration of exposure: 124, 118, 130, 95 wks respectively for 2.5mg, 5mg, 10 mg, pla ] [ Designated as safety issue: Yes ]
    AE=any new untoward medical occurrence or worsening of a pre-existing medical condition which does not necessarily have a causal relationship with this treatment. SAE=any untoward medical occurrence that at any dose: results in death, is life-threatening, requires inpatient hospitalization or causes prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, results in development of drug dependency or drug abuse, is an important medical event. Related events=relationship of certain, probable, possible, or missing.

  • Marked Laboratory Abnormalities - During ST + LT Treatment Period [ Time Frame: Lab assessments taken during and up to 14 days after the last dose of study drug during the ST + LT Treatment Period. Mean duration of exposure: 124, 118, 130, 95 weeks, respectively, for 2.5mg, 5mg, 10 mg, placebo. ] [ Designated as safety issue: Yes ]
    A laboratory value was considered a marked abnormality if it is outside the pre-defined criteria for marked abnormality and the on-treatment value was more extreme (farther from the limit) than the baseline value. Pre-Rx=pretreatment; ULN=upper limit of normal; ALP=alkaline phosphatase; AST=aspartate aminotransferase; ALT=alanine aminotransferase; unspec=unspecified; sodium serum low: <0.9 x Pre-Rx & <=130mEq/L / high: >1.1 x Pre-Rx & >=150mEq/L; potassium, serum low: <=0.8 x Pre-Rx & >=6.0mEq/L / high: 1.2 x Pre-Rx & >=6.0mEq/L; LLN=lower limit of normal.

  • Baseline and Changes From Baseline in Hemoglobin During the ST + LT Period [ Time Frame: Weeks 0, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 30, 37, 50, 63, 76, 89, 102, 115, 128, 141, 154, 167, 180, 193, 206 ] [ Designated as safety issue: Yes ]
  • Baseline and Changes From Baseline in Hematocrit During the ST + LT Period [ Time Frame: Weeks 0, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 30, 37, 50, 63, 76, 89, 102, 115, 128, 141, 154, 167, 180, 193, 206 ] [ Designated as safety issue: Yes ]
  • Baseline and Changes From Baseline in Red Blood Cell Counts (x 10^6 c/µL) During the ST + LT Period [ Time Frame: Weeks 0, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 30, 37, 50, 63, 76, 89, 102, 115, 128, 141, 154, 167, 180, 193, 206 ] [ Designated as safety issue: Yes ]
  • Baseline and Changes From Baseline in Platelet Counts (x 10^9 c/L) During the ST + LT Period [ Time Frame: Weeks 0, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 30, 37, 50, 63, 76, 89, 102, 115, 128, 141, 154, 167, 180, 193, 206 ] [ Designated as safety issue: Yes ]
  • Baseline and Changes From Baseline in White Blood Cell Counts (x 10^3 c/µL) During the ST + LT Period [ Time Frame: Weeks 0, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 30, 37, 50, 63, 76, 89, 102, 115, 128, 141, 154, 167, 180, 193, 206 ] [ Designated as safety issue: Yes ]
  • Baseline and Changes From Baseline in Absolute Neutrophil Counts (x 10^3 c/µL) During the ST + LT Period [ Time Frame: Weeks 0, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 30, 37, 50, 63, 76, 89, 102, 115, 128, 141, 154, 167, 180, 193, 206 ] [ Designated as safety issue: Yes ]
  • Baseline and Changes From Baseline in Absolute Lymphocyte Counts (x 10^3 c/µL) During the ST + LT Period [ Time Frame: Weeks 0, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 30, 37, 50, 63, 76, 89, 102, 115, 128, 141, 154, 167, 180, 193, 206 ] [ Designated as safety issue: Yes ]
  • Baseline and Changes From Baseline in Absolute Monocyte Counts (x 10^3 c/µL) During the ST + LT Period [ Time Frame: Weeks 0, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 30, 37, 50, 63, 76, 89, 102, 115, 128, 141, 154, 167, 180, 193, 206 ] [ Designated as safety issue: Yes ]
  • Baseline and Changes From Baseline in Absolute Basophil Counts (x 10^3 c/µL) During the ST + LT Period [ Time Frame: Weeks 0, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 30, 37, 50, 63, 76, 89, 102, 115, 128, 141, 154, 167, 180, 193, 206 ] [ Designated as safety issue: Yes ]
  • Baseline and Changes From Baseline in Absolute Eosinophil Counts (x 10^3 c/µL) During the ST + LT Period [ Time Frame: Weeks 0, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 30, 37, 50, 63, 76, 89, 102, 115, 128, 141, 154, 167, 180, 193, 206 ] [ Designated as safety issue: Yes ]
  • Changes From Baseline in Systolic Blood Pressure During the ST + LT Period [ Time Frame: Weeks 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 30, 37, 50, 63, 76, 89, 102, 115, 128, 141, 154, 167, 180, 193, 206 ] [ Designated as safety issue: Yes ]
  • Changes From Baseline in Diastolic Blood Pressure During the ST + LT Period [ Time Frame: Weeks 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 30, 37, 50, 63, 76, 89, 102, 115, 128, 141, 154, 167, 180, 193, 206 ] [ Designated as safety issue: Yes ]
  • Changes From Baseline in Heart Rate During the ST + LT Period [ Time Frame: Weeks 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 30, 37, 50, 63, 76, 89, 102, 115, 128, 141, 154, 167, 180, 193, 206 ] [ Designated as safety issue: Yes ]
  • Electrocardiogram (ECG) Tracings - Shift Table From Baseline (BL) to Selected Visits During ST + LT Treatment Period [ Time Frame: Baseline, Weeks 12, 24, 76, 102, 154, 206, ] [ Designated as safety issue: Yes ]
    The normality/abnormality of the ECG tracing was determined by the investigator.

  • All Reported Hypoglycemic Adverse Events During the ST + LT Treatment Period [ Time Frame: AEs: up to last treatment day + 1 day or last visit day in the ST+LT period; SAEs: up to last treatment day + 30 days or last visit day + 30 days in the LT+ST period. Mean duration of exposure: 124, 118, 130, 95 wks respectively for 2.5mg, 5mg, 10 mg, pla ] [ Designated as safety issue: Yes ]
    Hypoglycemic Events are based upon the Saxagliptin Predefined List of Events, which are hypoglycemia, blood glucose decreased, and hypoglycemic unconsciousness.

  • Confirmed Hypoglycemia During the ST + LT Treatment Period [ Time Frame: AEs: up to last treatment day + 1 day or last visit day in the ST+LT period; SAEs: up to last treatment day + 30 days or last visit day + 30 days in the LT+ST period. Mean duration of exposure: 124, 118, 130, 95 wks respectively for 2.5mg, 5mg, 10 mg, pla ] [ Designated as safety issue: Yes ]
    'Confirmed' = recorded on the hypoglycemia AE case report form with a fingerstick glucose <= 50 mg/dL and associated symptoms.


Enrollment: 1462
Study Start Date: August 2005
Study Completion Date: February 2010
Primary Completion Date: October 2006 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Saxagliptin + Metformin (A)
Pioglitazone 15-45 mg (as needed for rescue)
Drug: Saxagliptin + Metformin
Tablets, Oral, 2.5 mg Saxagliptin (plus flexible metformin dose), Once daily (24 weeks ST, 42 months LT)
Other Name: BMS-477118
Drug: Pioglitazone
Tablets, Oral, 15 - 45 mg (as needed for rescue)
Experimental: Saxagliptin + Metformin (B)
Pioglitazone 15-45 mg (as needed for rescue)
Drug: Saxagliptin + Metformin
Tablets, Oral, 5 mg Saxagliptin (plus flexible metformin dose), Once daily (24 weeks ST, 42 months LT)
Other Name: BMS-477118
Drug: Pioglitazone
Tablets, Oral, 15 - 45 mg (as needed for rescue)
Experimental: Saxagliptin + Metformin (C)
Pioglitazone 15-45 mg (as needed for rescue)
Drug: Saxagliptin + Metformin
Tablets, Oral, 10 mg Saxagliptin (plus flexible metformin dose), Once daily (24 weeks ST, 42 months LT)
Other Name: BMS-477118
Drug: Pioglitazone
Tablets, Oral, 15 - 45 mg (as needed for rescue)
Placebo Comparator: Placebo+ Metformin (D)
Pioglitazone 15-45 mg (as needed for rescue)
Drug: Placebo + Metformin
Tablets, Oral, 0 mg, Once daily (24 weeks ST, 42 months LT)
Drug: Pioglitazone
Tablets, Oral, 15 - 45 mg (as needed for rescue)

Detailed Description:

All subjects will participate in a lead-in period, and qualifying subjects will continue into a short-term randomized treatment period. Subjects who complete the short-term period will be eligible to enter the long term extension period. Also, subjects in the short-term period who have an elevated blood sugar that requires additional medication for blood sugar control will be eligible to enter the long-term treatment extension period where they will receive pioglitizone added onto their blinded study medication

  Eligibility

Ages Eligible for Study:   18 Years to 77 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Type 2 diabetes mellitus requiring treatment with at least 1500 mg but not greater than 2550 mg of a maximum tolerated dose of Metformin therapy for at least 8 weeks prior to screening.
  • HbA1c >= 7.0% and <= 10.0 %
  • Body mass index <= 40 kg/m2
  • Fasting C-peptide >= 1 ng/dL

Exclusion Criteria:

  • Symptomatic poorly controlled diabetes
  • Recent cardiac or cerebrovascular event
  • Serum creatinine >= 1.5 mg/dL for males and >= 1.4 mg/dL for females
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00121667

  Show 154 Study Locations
Sponsors and Collaborators
AstraZeneca
  More Information

Additional Information:
Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Study Director, Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT00121667     History of Changes
Other Study ID Numbers: CV181-014
Study First Received: July 18, 2005
Results First Received: March 15, 2011
Last Updated: June 4, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Pioglitazone
Saxagliptin
Metformin
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions
Incretins
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Dipeptidyl-Peptidase IV Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on August 20, 2014